Department of Clinical Physiopathology, University of Florence and Istituto Toscano Tumori, Florence, Italy.
Neuroendocrinology. 2010;92 Suppl 1:23-7. doi: 10.1159/000314312. Epub 2010 Sep 10.
PPAR-γ is a member of the nuclear hormone receptor superfamily of transcription factors, whose thiazolidinedione ligands (TZD) have been recently demonstrated to also possess anticancer properties in addition to their well-known insulin-sensitizer and glucose/lipid regulation activity. In this minireview, we summarize the current knowledge on PPAR-γ in normal and tumoral corticotropic pituitary and adrenal cells. The receptor expression has been shown in ACTH-secreting cells in both normal and adenomal pituitary as well as in normal and tumor adrenal cortex. Preclinical studies conducted both in vitro on tumor cells and in vivo on xenograft tumor models obtained by subcutaneous injection of cancer cells have evidenced the anticancer properties of TZD, in particular rosiglitazone (RGZ) and pioglitazone (PIO). In both pituitary and adrenocortical cancer, RGZ treatment results in inhibition of cell proliferation, through G0/G1 cell-cycle arrest and induction of cell apoptosis, leading to significant inhibition of tumor growth in the xenograft tumor models. In addition, since RGZ can reduce ACTH and corticosterone secretion in mouse corticotropic pituitary tumors, both RGZ and PIO have been used in the treatment of Cushing's disease with variable but generally unsatisfactory results. Discrepancies in the antitumor effects of TZD observed between successful preclinical and unsuccessful clinical studies may be particularly due to differences in treatment duration and doses used.
过氧化物酶体增殖物激活受体-γ（PPAR-γ）是核激素受体超家族转录因子的成员，其噻唑烷二酮配体（TZD）除了具有众所周知的胰岛素增敏和葡萄糖/脂质调节作用外，最近还被证明具有抗癌特性。在这篇综述中，我们总结了 PPAR-γ 在正常和肿瘤性促肾上腺皮质激素分泌垂体和肾上腺细胞中的现有知识。该受体在正常和腺瘤性垂体中的 ACTH 分泌细胞以及正常和肿瘤性肾上腺皮质中均有表达。在体外对肿瘤细胞进行的临床前研究和通过皮下注射癌细胞获得的异种移植肿瘤模型进行的体内研究均证明了 TZD，特别是罗格列酮（RGZ）和吡格列酮（PIO）的抗癌特性。在垂体和肾上腺皮质癌中，RGZ 治疗通过 G0/G1 细胞周期阻滞和诱导细胞凋亡导致细胞增殖受到抑制，从而导致异种移植肿瘤模型中的肿瘤生长显著抑制。此外，由于 RGZ 可降低小鼠促肾上腺皮质激素分泌性垂体肿瘤中的 ACTH 和皮质酮分泌，因此 RGZ 和 PIO 已被用于治疗库欣病，但结果差异很大，通常并不令人满意。TZD 的抗肿瘤作用在成功的临床前研究和不成功的临床研究之间观察到的差异可能特别归因于治疗持续时间和使用剂量的差异。
